The use of corticosteroids in the treatment of inflammatory conditions has been limited primarily due to their systematic suppressive effects on the adrenal function and the immune system. To overcome this limitation, a focused effort has been made to synthesize locally active anti- inflammatory steroids without systemic adverse effects based on the antedrug concept. In this approach, antedrugs are designed to exert their actions at the application site, but to undergo the systemic circulation. Thus, the true antedrug acts locally and is devoid of systemic adverse effects. It is proposed to synthesize a new group of steroidal antedrugs and evaluate them comprehensively with respect to their local to systemic pharmacological activities. To further delineate the mode of action of the new steroids, their receptor binding characteristics, effects on pituitary adrenal function, glycogen deposition, liberation of prostanoids and nitric oxide (NO) will be studied. Results of these studies will yield valuable insight into the structural characteristics for the maximum separation of local anti-inflammatory activity from systemic adverse effects, and the mode of action of these non-systemic anti-inflammatory steroids with the promise of providing a solid rational basis for development of new potent anti-inflammatory steroids devoid of systemic side effects.